Activation of benzo(a)pyrene-7,8-dihydrodiol in rat uterus: an in vitro study.
Peroxidatic metabolism of benzo(a)pyrene-7,8-dihydrodiol by calcium containing extracts of rat uteri was investigated. Covalently bound and soluble metabolites of benzo(a)pyrene-7,8-dihydrodiol were quantitated by radiometry and high performance liquid chromatography, respectively. 1. Uterine extracts incubated with benzo(a)pyrene-7,8-dihydrodiol activated this proximate mutagen to protein binding metabolite(s). 2. Hydrogen peroxide increased the protein binding and yielded a substantial amount of benzo(a)pyrene-trans-anti-tetrahydrotetrol, suggesting the peroxyl-type free-radical epoxidation process. 3. The results indicate that rat uterine peroxidase is able to catalyze free-radical activation of benzo(a)pyrene-7,8-dihydrodiol by epoxidation to its 9,10-dihydrodiolepoxide, a known ultimate mutagen and carcinogen.
Byczkowski
J Z
JZ
Toxicology Program, College of Public Health, University of South Florida, Tampa 33612.
Kulkarni
A P
AP
D000818:Animals; D001711:Biotransformation; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004101:Dihydroxydihydrobenzopyrenes / Q000493:pharmacokinetics*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000378:metabolism*
D004101:Dihydroxydihydrobenzopyrenes; D011506:Proteins; C017228:benzo(a)pyrene 7,8-dihydrodiol; D006861:Hydrogen Peroxide; D002118:Calcium